Proteasome inhibitors prevent cytochrome c release during apoptosis but not in excitotoxic death of cerebellar granule neurons

FEBS Letters

Petragallo, Vito²  Atlante, Anna²  Calissano, Pietro¹  Canu, Nadia¹  Marra, Ersilia²  Bobba, Antonella² 

[1] Isituto di Neurobiologia e Medicina Molecolare, CNR, Viale Marx 15, 00137 Rome, Italy;Centro di Studio sui Mitocondri e Metabolismo Energetico, CNR, Via Amendola 165/A, 70126 Bari, Italy

关键词: Cytochrome c;    Proteasome;    Apoptosis;    Necrosis;    Cerebellar granule cell;    BME;    basal medium with Eagle's salts;    CGC;    cerebellar granule cell;    S-K25;    control CGCs for the apoptotic paradigm;    S-K5;    apoptotic CGCs;    C-CGC;    control CGCs for the necrotic paradigm;    GLU-CGC;    necrotic CGCs;    cyt c;    cytochrome c;    MK801;    (+)-5-methyl-10;    1-dihydro-5H-dibenzo(a;    d)cyclohepten-5;    10-imine hydrogen maleate;   

DOI  :  10.1016/S0014-5793(02)02231-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In order to find out whether and how proteasomes participate in the processes leading cerebellar granule cells to death either in necrosis, due to glutamate neurotoxicity, or in apoptosis, due to K⁺ shift, we measured the three proteasome activities by using specific fluorescent probes and investigated the effect of several proteasome inhibitors, including MG132, on the cytochrome c release taking place in the early phase of both apoptosis and necrosis. We show that differently from apoptosis, the early phase of necrosis does not require proteasome activation. Inhibition of proteasome activity can prevent cytochrome c release in cerebellar granule cells undergoing apoptosis, thus improving cell survival, but not necrosis. These findings show that proteasomes play an important role in the early phase of apoptosis but not that of necrosis, and that these two types of cell death differ from each other in their mechanism of cytochrome c release.

【 授权许可】

Unknown